Figure 2.

Genomic and non-genomic pathways of estrogen receptors (ERs). ERs can act through genomic pathways and nongenomic pathways. The nongenomic pathways may also result in the transcriptional activation of genes. (1) Classic pathway: dimerization of ERs triggered by the binding of E2, followed by nuclear translocation to regulate the transcriptional activity of genes bearing the estrogen response element (ERE). (2) ER activity independent of ERE: the recognition of promoters result from the protein−protein interaction of ERs with other transcription factors (TF). (3) Ligand-independent activity: the binding of growth factors to membrane receptors triggers protein kinase cascades that activate ERs by phosphorylation, promoting their nuclear translocation and recognition of the ERE in target genes. (4) Nongenomic pathway: the binding of the ligand causes mER and GPER1 to initiate signaling pathways, which promote the activation of enzymes and transcriptional factors that can regulate the transcription of diverse genes. ER, estrogen receptors; mER, membrane estrogen receptors; TF, transcription factor; ERE, estrogen response element; non-ERE, other transcription factors distinct from ERE; P, phosphorylated receptor; G, G protein-coupled receptor; GPER, G protein-coupled estrogen receptor; cav, caveolin.